rs2273797

Positions:

• chr11-33864534-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005574.4(LMO2):​c.464+68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,329,298 control chromosomes in the GnomAD database, including 24,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3307 hom., cov: 32)
  • Exomes 𝑓: 0.19 (21492 hom.)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

Genes affected

LMO2 (HGNC:6642): (LIM domain only 2) LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.464+68G>A		intron_variant		ENST00000257818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.464+68G>A		intron_variant		1	NM_005574.4
LMO2	ENST00000395833.7	c.257+68G>A		intron_variant		1		P1
LMO2	ENST00000411482.1	c.*201+68G>A		intron_variant, NMD_transcript_variant		1
LMO2	ENST00000464025.5	n.550+68G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31049 AN: 151906 Hom.: 3300 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.186 AC: 219215 AN: 1177274 Hom.: 21492 AF XY: 0.189 AC XY: 111228 AN XY: 587092

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.204 AC: 31079 AN: 152024 Hom.: 3307 Cov.: 32 AF XY: 0.209 AC XY: 15541 AN XY: 74314

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.204

Alfa AF: 0.185 Hom.: 3502

Bravo AF: 0.203

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2273797; hg19: chr11-33886080; COSMIC: COSV57648079; COSMIC: COSV57648079;